Must use wisely

15th of April 2010

At the end of last year newspapers featured a story about research carried out in Ireland which suggested that disinfectants used in hospitals can actually increase the growth of fatal ‘superbugs’. This research had concluded that bugs are able to become resistant to disinfectants which are meant to kill them. Not only that, they can develop immunity to one of the most commonly prescribed antibiotics – ciprofloxacin – without even being exposed to the drug. ECJ looks more closely at the study and also presents its findings to experts at Diversey, which develops professional disinfectants.

Carried out by the Department of Microbiology, School of Natural Sciences, at the National University of Ireland in Galway, the study was devised to investigate the link between adaptation to biocides and antibiotics in Pseudomonas aeruginosa. This is an opportunistic bacterium that causes a wide range of infections in people with weak immune systems - it is an important cause of hospital-acquired infections.

Bacteria are constantly challenged by a gradient of biocide concentration from a subinhibitory level up to an inhibitory level in domestic and healthcare environments. There is increasing concern that the use of biocides [such as benzalkonium chloride (BKC) and other quaternary ammonium compounds] in these environments may be contributing to the development of microorganisms with decreased susceptibilities to antibiotics and disinfectants. There is some evidence to suggest micro-organisms that have become less sensitive to disinfectants - because of exposure to biocides - also show decreased susceptibilities to some antibiotics.

BKC is a nitrogen-based quaternary ammonium compound demonstrating broad-spectrum antimicrobial activity. Some adaptation to the biocide has been noted in strains of Pseudomonas aeruginosa, and a principal aim of this research was to determine if subjecting populations of P. aeruginosa NCIMB 10421 to increasing levels of BKC selection pressure in long-term continuous culture would result in cross-adaptation to antimicrobials.

In the laboratory, researchers added low levels of the disinfectant to a solution that included the bacteria. They found the bacteria mutated and became resistant to the powerful antibiotic ciprofloxacin after being exposed to the disinfectant. The bacteria also became resistant to the disinfectant.

At the high concentration levels generally used this was unlikely to be a problem but "in principle this means residue from incorrectly diluted disinfectants left on hospital surfaces could promote the growth of antibiotic-resistant bacteria", said Dr Gerard Fleming who led the study. "What is more worrying is that bacteria seem to be able to adapt to resist antibiotics without even being exposed to them."

Dr Fleming stressed he is not suggesting there is anything wrong with using disinfectants - they should just be used properly. "It is acceptable to use disinfectants and they can be highly effective, but do not misuse them or overuse them," he told ECJ. "It is vital they are used in the correct concentration and given the necessary contact time."

Of course this research took place in a laboratory, not in a real hospital environment. ECJ invited Diversey, which develops disinfectants for a wide range of applications, to read the study in full and comment on the conclusions. We spoke to Meredith Theelen, R&DE scientist, and Paul Hill, global RD&E director kitchen care, fabric care and personal care solutions - asking them first to comment generally on how the research was carried out.

"In this study, a lot of effort has been taken to grow a specific, adapted strain of micro-organism. The study looks thorough and is carried out under precisely controlled laboratory conditions which would be unlikely to occur in practice when the recommendations for application are followed correctly."

The level of BKC exposed to Pseudomonas strains is at a lower dilution, below those recommended in many disinfectants. It seems that the authors took a theoretical approach because disinfectants deal with bacteria outside the human body eg, on surfaces, whereas antibiotics are aiming at bacteria in the body."

Has Diversey carried out an investigations into this particular area itself? "It is very important for Diversey to offer the right formulations for the right needs. It is common knowledge that not all disinfectants are formulated to fight all bugs. Diversey has been working on high technology innovation to create and improve wide spectrum and effective disinfectants for many years.

"Our product Oxivir, which relies on AHP (Accelerated Hydrogen Peroxide) technology is a solid example to this. In the very same manner, the hand washing disinfectant Sensisept utilises chlorhexidine and our expertise in hand care to provide a wide spectrum disinfectant with long lasting effect while being as mild as water for the hands.

"We closely follow the scientific literature in this area and have seen no evidence that would lead us to conclude that correct use of our disinfectant products would have any adverse effect as described in this study."

Has the company ever found evidence that certain bacteria can become resistant to the disinfectants that are meant to kill them, and in turn to antibiotics? "Disinfectant chemistries have been in use in industry for decades and we have never recovered bacterial strains in practice that are resistant to disinfectants," said Theelen.

So has Diversey carried out studies into the use of its own disinfectants in hospitals? "As Diversey, we are proud to say that we have an evolving know-how in all areas of cleaning and hygiene. We aim to be at the leading edge with innovation and new developments. That does not necessarily dictate that we have to find out things on our own, but we aim to create close contact with industry experts as well.

"All of our disinfectants have been tested by external laboratories to fulfill the criteria as laid down in internationally recognised standard testing protocols for disinfectant usage. Disinfectants used as recommended do effectively kill the strains of bacteria required and therefore the generation of resistance under these circumstances is very unlikely."

So should the findings of the University of Ireland study be of great concern to those responsible for cleaning and infection control in hospitals? The Diversey experts think not. "It is unlikely these types of adapted strains could form in practice. There must be a persistent wet environment for these types of gram-negative (Pseudomonas) strains to thrive. Our disinfectant usage instructions call for correct dosage and contact time and further we take efforts to train cleaning staff on proper cleaning methods. Following disinfection, clean surfaces will be left to dry; therefore it would be highly unlikely this specific strain would be able to adapt in this type of environment."

Should there be a fundamental review of how disinfectants are used in hospitals? "Precisely. One should keep in mind that use of disinfectant products will not reduce the risks on their own unless the prescribed application method is followed through," explained Hill. "Contact time is especially the pressing issue here as operators are constantly challenged by their efficiency. Diversey outlines very specific disinfectant usage conditions that are not in line with what is proposed in this study. The conditions specified in this study are not reflecting what is actually occurring in the normal hospital environment."

Finally, what would their advice be to anyone using disinfectants in such hygiene-critical areas as hospitals? "For effective infection control, disinfectants should be used for targeted hygiene, ie, only there where it is required instead of widespread usage. One should always take into account the level of dirt/soil. Under very dirty conditions a cleaning step may need to precede the actual disinfection. Under slightly soiled conditions the use of a combined detergent-disinfectant is an optimal choice, whereas under clean conditions a disinfectant alone may suffice.

"In all cases it is essential that the right recommended dosage and contact time are being applied as laid out on the manufacturer’s instructions. Diversey is there as a resource for infection control specialists. Since every cleaning situation is unique, we encourage them to contact us about proper cleaning and disinfection procedures, methods for cleaning and when/where to use efficacy-approved products."

Hill and Theelen concluded: "We have to keep in mind that there remains a huge risk for re-infection unless proper processes for cleaning and disinfection are completely followed. This factor needs to be monitored closely in every healthcare environment so that the effort of doctors who do their best to cure illness does not go in vain."

Dr Fleming agreed there needed to be further studies into how disinfectants were used in hospitals and how antibiotics were prescribed. "We also need to look at other organisms and other disinfectants," he explained. "However this study does illustrate something we should be concerned about. Disinfectants are our first line of defence against harmful germs, and antibiotics are the second line of defence in case of infection. We have shown that it is possible to corrupt both of those lines.

"If we can now examine how organisms become resistant to disinfectants we may be able to design disinfectants in the future that block this action inside the cell."

What would his advice be to those responsible for infection control within hospitals? "The best disinfectant solutions are those that have multiple forms of action," Dr Fleming replied. "I would suggest rotating the use of different disinfectants. On a broader level, I would advocate the tailoring of disinfectants to particular environments when necessary - that means taking swabs, culturing them and testing before selecting a disinfectant."

What this study highlights is just how crucial it is that cleaning staff in healthcare applications are briefed and trained sufficiently in the correct use of disinfectants. Dosage and contact time recommendations must be adhered to in order to maintain that valuable line of defence.